The objective of this project is to induce diabetes in pregnant rats and study the effects of maternal diabetes mellitus on the developmental changes in carbohydrate metabolism in livers of fetuses and newborn rats. Specifically, alterations in hepatic glycogen levels and blood metabolites as well as induction of phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme, in developing liver are being investigated. Newborns of mild diabetic rats experience severe hypoglycemia during the first two postnatal hours compared with pups of normal and severe diabetic rats. An initial reduction in hepatic glycogen in newborns diabetic rats in the immediate postnatal period was delayed compared with pups of normal animals. Studies in which hepatic phosphoenolpyruvate carboxykinase activity and synthesis were studied, it was observed that the activity and the rate of synthesis of the enzyme were lower in livers from neonates of diabetic mothers during the first 9 hours as compared with age-matched pups of normal rats. In normal newborns, injection of glucose at 3 hour intervals starting at birth caused a reduction in the postnatal increase in PEP-carboxykinase activity and synthesis. Also, administration in utero of insulin or glucose to the term fetuses caused a reduction in premature induction by c-AMP of hepatic PEP-carboxykinase in fetuses of both diabetic and normal rats. Our findings show that there is a delayed in the emergence of hepatic PEP-carboxykinase in newborns of diabetic rats. This delay may also be manifested in the initiation of gluconeogenesis of neonates of diabetic mothers.